Based on improved safety and efficacy results, advanced colorectal cancer (CRC) treatment has recently shifted from intravenous bolus 5-fluorouracil (5-FU) monotherapy to standard combinations of prolonged intravenous 5-FU infusion with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). Capecitabine, a rationally designed oral fluoropyrimidine that is converted into 5-FU preferentially at the tumor site, could replace infusional 5-FU as the mainstay of combined chemotherapy treatment for metastatic CRC. Evidently, oral medication obviates the drawbacks of prolonged intravenous infusion. The combination of capecitabine and oxaliplatin is especially attractive owing to its favorable tolerability profile, good activity and convenient administration schedule. Phase III trials comparing capecitabine/oxaliplatin with infusional regimens of 5-FU +/- LV and oxaliplatin in advanced CRC show similar toxicity and efficacy outcomes with both regimens. Capecitabine has the potential to replace 5-FU/LV as the optimal combination partner for oxaliplatin at a higher cost. Capecitabine and oxaliplatin concomitantly with radiation therapy has been evaluated before surgery in rectal cancer treatment. The combination of capecitabine and oxaliplatin, with or without bevacizumab, a monoclonal antibody blocking VEGF, is also being evaluated in early stage colon cancer.